This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Overview: The overall goal of this project is to develop new methods for quantitative measurements of cerebral blood flow (CBF) and arterial transit time (ATT), also called bolus arrival time (BAT) in arterial spin labeling perfusion studies for specific applications to support the research projects and clinical applications of the Resource Center. Arterial spin labeling (ASL) MRI has great promise for quantitative measurements of brain function, because the method is entirely non-invasive and can be repeated rapidly and in principle indefinitely. Over the past decade, the investigator of this project has developed new 3D acquisition methods resulting in higher efficiency, sensitivity, and precision. This application to create new cycled labeling methods represents new efforts to develop improved acquisition techniques focused on the detection of neurodegenerative diseases. Specific Aim1: Develop Dynamic ASL with multi-bolus Hadamard encoding: Resent results show ATT measured in time series ASL images may be a useful biomarker in differentiating mild cognitive dementia for Alzheimer's disease. The time coarse data is obtained by repeating the ASL measurements with incremented TI to obtain signal time curves. A novel cycled labeling scheme will encode flow changes with multiple pulsed boli within each of several cycles of ASL image acquisition. We will develop a novel method of Hadamard encoding in cycled ASL sequences to obtain many boli of shorter durations and to obtain several times higher SNR or reduce acquisition time and improved curve fitting of different vascular compartments to evaluate dynamic signal. Specific Aim 2: Development of Multiple-Echo 3D GRASE Acquisition: We aim to extend 3D ASL GRASE to dual-echo and multiple echo time (TE) acquisitions that provide the T2-relaxation parameterization of the ASL signal. To obtain this information, we will develop well controlled pulse sequences timing changes utilizing both single acquisition and multiple data acquisitions with an encoded variable TE parameters. eter.